Human milk and breast feeding has become increasingly popular for its recognized beneficial properties as a nutritional source, in mother-child bonding, and more recently for providing host defense factors which can provide essential protection during the neonatal period against infection. However, little is known on the effects of human milk on immune function and development in the premature infant. The major objective of this proposal is to define the effects of human milk on the function and development of the immune system of the premature infant equal to or less than 1500 g. Two groups of premature infants, equal to or less than 1500 g will be studied prospectively in the Neonatal Intensive Care Unit: one group fed mother's breast milk and the other a proprietary formula. Serum immunoglobulins (Ig) and complement components (C3, C4, Factor B, Factor D) will be quantitated comparing milk-fed and formula-fed infants to determine the effect(s) of the type of feeding on the development of Igs and complement. Secretory IgA, specific IgA antibodies to E coli Kl antigen, and the heat stable opsonins to E coli and S aureus will be measured in the serum of the premature infant to determine if these immune factors are passively transferred by human milk to the premature infant. Since breast milk may also contain factors which can transfer adaptive immunity or modulate immune function, in vitro B-cell function as measured by mitogen-induced B-cell differentiation into antibody secreting cells will be studied in premature infants. T-cell subpopulations using defined monoclonal antibodies (OKT4, OKT3, OKT8) will be quantitated in premature infants to determine the effects of human milk on the development of regulatory T-cell subsets. The premature infant groups will also be studied at 2, 4 and 8 months following discharge from the NICU to determine the effects of the type of feedings on the maturation of the immune system during the first year of life. Because of their prematurity and associated medical problems, premature infants are compromised hosts. The studies outlined in this proposal are important in delineating the properties of human milk which offer a special advantage over formula in providing immunological factors important in protecting the premature infant against infection.